It is proposed to investigate the mechanisms by which the chronic interference of transmission between neurons and their effector cells, including other neurons, results in an enhanced sensitivity of the effector cells. The effector cells studied will include smooth muscle, cardiac muscle and central neurons. Specifically, it is proposed to: 1. Characterize the nature of calcium binding and release by subcellular components of normal and supersensitive smooth muscle. 2. Determine the role of ouabain-sensitive Na ion, K ion-ATPase in postjunctional supersensitivity in all of the tissues. 3. Investigate, by means of microelectrodes, the changes in membrane electrical properties which are associated with supersensitivity in atrial cells, especially pace-maker cells, and determine if an alteration in the activity of an electrogenic component of the Na ion, K ion-pump is a contributing factor.